The MOMENT Trial: Mevrometostat Plus Enzalutamide in Post‑ARPI, Pre‑Abiraterone mCRPC

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Mevrometostat is an oral EZH2 inhibitor being developed to overcome resistance to androgen‑receptor–targeted therapy in prostate cancer. In tumors, EZH2 helps switch off tumor‑suppressor genes and supports androgen‑independent growth and lineage plasticity, changes that are strongly linked to progression on drugs like enzalutamide. Adding an EZH2 inhibitor to continued AR blockade is meant to “re‑discipline” […]

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Phase 3 CaBRA Trial: Adding Carboplatin for mHSPC With BRCA Mutations or Neuroendocrine Phenotype

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In the phase 3 CaBRA trial, carboplatin is added to the docetaxel-based chemotherapy backbone used with lifelong ADT (androgen deprivation therapy) and darolutamide,  creating a quadruple-intensification  therapy for a small but very high-risk subgroup of metastatic castration-sensitive prostate cancer. The trial focuses on tumors with either BRCA alterations or neuroendocrine differentiation, two features that are […]

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B7-H3 ADC YL201 Delivers Encouraging Results in Advanced mCRPC

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YL201, a B7-H3–targeting antibody–drug conjugate, is showing notable activity in advanced metastatic castration-resistant prostate cancer (mCRPC), including patients who have progressed after androgen receptor–targeted therapy and chemotherapy. In a phase 2 study of 82 heavily pretreated patients, the drug delivered a confirmed PSA50 response rate of 38.5%, an objective response rate of 29.5%, and a […]

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Phase 1/2 Trial: Epigenetic KAT6 Inhibitor Plus Darolutamide in mCRPC

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A Phase 1b/2 trial is planned to test the investigational KAT6 inhibitor OP-3136 combined with darolutamide in metastatic castration-resistant prostate cancer (mCRPC). About 36 patients will be enrolled, with the study expected to start in the second half of 2026. The focus is on safety, tolerability, and early signs of anti-tumor activity. OP-3136 blocks KAT6A/B, […]

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A-DREAM Trial Suggests Some Men with Metastatic Prostate Cancer May Stop Therapy Safely for a Time

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A new phase 2 study, A-DREAM / Alliance A032101, suggests that a carefully selected group of men with metastatic hormone-sensitive prostate cancer may be able to interrupt androgen deprivation therapy and an androgen receptor pathway inhibitor after achieving an excellent response, while still maintaining a treatment-free interval. The study met its primary endpoint, with 41% […]

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Phase 2 TALENT Trial: Talazoparib as Monotherapy or With Enzalutamide in HRR-deficient mCRPC

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The TALENT trial is a randomized, open‑label, phase 2 trial evaluating whether adding enzalutamide to talazoparib improves outcomes compared with talazoparib alone in men with metastatic castration‑resistant prostate cancer (mCRPC) who have homologous recombination repair (HRR) gene alterations and have progressed after abiraterone‑based therapy. The trial builds on the phase 3 TALAPRO‑2 results, which showed […]

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ABBV-969 in mCRPC: Dual‑Targeting ADC Shows Robust PSA and Objective Responses in Heavily Pretreated Patients

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ABBV-969, a first-in-class dual-targeting antibody-drug conjugate (ADC), is emerging as a promising new therapeutic candidate for patients with metastatic castration-resistant prostate cancer (mCRPC), particularly in the late-line setting where treatment options are limited and outcomes remain poor. Designed to simultaneously target prostate-specific membrane antigen (PSMA) and six-transmembrane epithelial antigen of prostate 1 (STEAP1), both highly […]

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CONVERGE-01: CONV01-α Shows Activity After Lu-PSMA in mCRPC

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Actinium-225 rosopatamab tetraxetan (CONV01-α) is a PSMA-targeted alpha radioligand therapy being tested in men with metastatic castration-resistant prostate cancer who have already received androgen receptor pathway inhibitors, up to one taxane regimen, and 1–6 cycles of lutetium-177 PSMA therapy (Pluvicto), with all patients having PSMA PET–positive disease by VISION criteria. The drug links an alpha […]

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Overcoming AR Mutations in Prostate Cancer: Phase 1 Results of HRS-5041

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A new investigational drug, HRS-5041, may offer a compelling strategy to overcome resistance to androgen receptor (AR)-targeted therapies.. Unlike traditional AR inhibitors, HRS-5041 is an oral androgen receptor degrader designed to eliminate the receptor itself, including clinically relevant mutant forms. In a phase 1, 156 patients with mCRPC were treated with HRS-5041. All patients had […]

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BAT Before Sipuleucel-T in mCRPC: Immune Priming?

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Bipolar androgen therapy (BAT) given before sipuleucel‑T appears to increase the rate and magnitude of PA2024‑specific immune responses in men with metastatic castration‑resistant prostate cancer (mCRPC), compared with historical sipuleucel‑T data. The central interpretation is not that BAT by itself generates this immune response, but that BAT may prime the tumor and immune environment so […]

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